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Biomedical subjects

D Webster

Publications and source records attributed to D Webster.

At least 37 records · Page 2Linked to original sources

Comparisons of magnitude estimation scaling of rock music by children, young adults, and older people.

The present study concerned the perceptual processing of complex auditory stimuli in 10 children (M age = 8.1) as compared to 10 young adults (M age = 19.3) and 10 older adult subjects (M age = 54.2). The auditory stimulus used was 10 sec. of rock music (Led Zeppelin, 1969). All three groups provided numerical responses to nine intensities of the rock music stimulus (10, 20, 30, 40, 50, 60, 70, 80, 90 dB above threshold). Analysis showed that the children reported a wider range of numerical responses than both adult groups. The mean numerical responses for the children ranged from .54 to 54.24. For the young adults the range was .76 to 11.37, and for the older subjects it was 1.6 to 23.31. Results suggest that the children were not bound by the same set of rules as the adults with regard to magnitude estimation scaling of the loudness of the rock music stimulus. Their internal scaling mechanisms appeared to be more flexible and broader based than those of the adults who participated in this study.

Acoustic Stimulation↗

High prevalence of thymic tissue in adults with human immunodeficiency virus-1 infection.

The thymus in adults infected with the HIV-1 is generally thought to be inactive, both because of age-related involution and viral destruction. We have revisited the question of thymic function in adults, using chest-computed tomography (CT) to measure thymic tissue in HIV-1-seropositive (n = 99) or HIV-1-seronegative (n = 32) subjects, and correlating these results with the level of circulating CD4(+) and CD8(+) T cells that are phenotypically described as naive thymic emigrants. Abundant thymic tissue was detectable in many (47/99) HIV-1-seropositive adults, aged 20-59. Independent of age, radiographic demonstration of thymic tissue was significantly associated with both a higher CD4(+) T cell count (P = 0.02) and a higher percentage and absolute number of circulating naive (CD45RA+CD62L+) CD4(+) T cells (P < 0.04). The prevalence of an abundant thymus was especially high in younger HIV-1-seropositive adults (</= 39 yr) with CD4 counts in the range 300-500 cells/microl and in older subjects (> 40 yr) regardless of CD4 count (P = 0.03). These studies suggest that the thymus is functional in some but not all adults with HIV-1 disease.

Acquired Immunodeficiency Syndrome↗

Comparison of the rate of sequence variation in the hypervariable region of E2/NS1 region of hepatitis C virus in normal and hypogammaglobulinemic patients.

The hypervariable region (HVR) of the E2/NS1 region of hepatitis C virus (HCV) varies greatly between viral isolates with high rates of genomic change reported during the course of chronic infection. The HVR is thought to encode a structurally unconstrained envelope protein containing several linear B cell epitopes recognized by neutralizing antibody. It has been postulated that amino acid changes in the HVR could result from humoral immune pressure leading to the selection of escape mutants. The aim of this study was to compare the rates of nucleotide and amino acid variation in the HVR of control patients to patients with common variable immunodeficiency (CVID) where the effect of the humoral immune system is reduced. Five controls and four patients with CVID were studied. Serum samples were taken over periods of between 1 and 6 years. HCV was detected by polymerase chain reaction (PCR) with primers derived from conserved flanking regions of the HVR. PCR products were cloned into a plasmid vector and recombinant clones identified by restriction enzyme digestion. Purified DNA from at least three individual clones from each time point was sequenced by the dideoxynucleotide chain-termination method. Consensus sequences were extracted from the three clones, and the DNA and deduced protein sequences were compared. Control patients had a mean rate of nucleotide change of 6.954 nucleotide substitutions per year, compared with patients with CVID with a rate of 0.415 nucleotide substitutions per year (P < .02). The corresponding rates for amino acid variation were 3.868 amino acid substitutions per year for the control patients compared with 0.185 amino acid substitutions per year for the patients with CVID. These findings suggest that in the absence of humoral immune selective pressure, the frequency of occurrence of genetic variation in the major viral species is reduced. The mutations occur, but in the absence of immune selection remain as minor species. The evolution of viral mutants capable of evading the host's immune system may contribute to the ability of HCV to establish chronic infection.

Adult↗

An ecological model for school-based mental health services for urban low-income aggressive children.

An ecological model for school-based mental health services that targets urban low-income aggressive children--a highly vulnerable and underserved population--is presented. The goals of the model are to increase children's and teachers' involvement in the delivery of services and to increase the integration of these services into existing school resources and activities. The model proposes that mental health service providers work in collaboration with teachers to deliver services that (1) can be managed by existing school resources and personnel, (2) are related to empirically based factors associated with reduced aggression and increased social functioning, and (3) are group administered to increase the number of children served and to reduce stigmatization associated with mental health services. The model is individualized and flexible by acknowledging that contexts for aggression differ across classrooms and children and by providing services specific to those contexts. Two studies are presented illustrating the application of this model to decrease aggression and increase academic engagement in low-income urban public schools.

Achievement↗

Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene.

X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.

Antigens, CD↗

SPECT (HMPAO) support for activation of the medial prefrontal cortices during toe graphaesthesia.

This experiment was designed to test the construct validity of psychometric analyses that suggested a strong functional association between the accuracy for toe graphaesthesia and selective activation of neurons within the medial prefrontal regions. Single Photon Emission Computerized Tomography (SPECT) profiles were obtained for three volunteers (2 men, 1 woman) after they had been exposed to a toe graphaesthesia task or had been exposed to the control setting. The two measurements for each participant were separated by at least one week. Qualitative evaluation, using criteria employed for clinical diagnoses, of serial coronal, sagittal, and horizontal sections clearly indicated a specific increase in uptake of tracer within the rostral one-third to one-half of the medial prefrontal cortices of all three subjects during the toe graphaesthesia task compared to that during baseline conditions. The results are consistent with our neuropsychological research which indicates that toe graphaesthesia may be an accurate and useful indicator of the functional integrity of the medial surfaces of the anterior cerebral hemispheres.

Adult↗

Orbital psuedotumour with intracranial extension. A case report.

Inflammatory pseudotumour of the orbit is an unusual condition of unknown aetiology which rarely extends beyond the orbit. To our knowledge 19 cases with intracranial extension have been reported, none of which involved the pituitary fossa or sphenoid sinus. Most required cytotoxic agents, surgery or radiotherapy in addition to corticosteroids. We present a case of orbital pseudotumour with extension into the pituitary fossa, sphenoid sinus and cavernous sinuses with vascular compression. Marked clinical improvement occurred on steroid therapy alone.

Adult↗

FT Raman microscopy of untreated natural plant fibres.

The application of FT-Raman microscopy to the non-destructive analysis of natural plant fibres is demonstrated with samples of flax, jute, ramie, cotton, kapok, sisal and coconut fibre. Vibrational assignments are proposed and characteristic features of each material are presented. Samples were not pre-treated chemically before analysis and were used directly from their respective storage collection; the adaptation of the Raman microscopic technique to the identification of specimens of natural fibres in archaeological burial sites is explored for its forensic potential.

Cellulose↗

Sedation, analgesia, and anesthesia issues in the pediatric patient.

Pediatric and adolescent patients facing analgesia, anesthesia, and surgical procedures require different considerations than adults do. The preoperative, intraoperative, and postoperative time periods are discussed. Analgesia considerations outside the operating room are covered. The practicing podiatric physician will be able to assess better the physical needs of the pediatric patient by understanding and incorporating their emotional needs.

Adolescent↗

Hematopoietic potential of cryopreserved and ex vivo manipulated umbilical cord blood progenitor cells evaluated in vitro and in vivo.

The hematopoietic potential of cryopreserved and ex vivo manipulated umbilical cord blood (UCB) samples was evaluated in vitro and in vivo. Phenotypic analysis shows that approximately 1% of cord blood mononuclear cells express high levels of CD34 antigen on their surface (CD34hi), but none of a panel of lineage antigens (Lin-), suggesting that they are hematopoietic progenitor cells that have not yet committed to a specific lineage. Approximately 1% of CD34hi/Lin- cells are primitive hematopoietic progenitors that produce B lymphoid and multiple myeloid progeny for up to 7 weeks in stromal cell cultures. Twenty-one percent (+/- 13%) of CD34hi/Lin- cells also express low levels of the Thy-1 antigen and are threefold to fourfold enriched over CD34hi/Lin- cells in primitive hematopoietic potential as measured by long-term culture and phenotypic analysis. One-week liquid cultures of CD34-enriched UCB progenitor cells in the presence of interleukin (IL)-3, IL-6, and stem cell factor (SCF) results in a two-fold to threefold expansion of progenitors capable of reinitiating long-term stromal cell cultures. Only the CD34hi/Thy-1+/Lin- cell population was capable of maintaining progenitors with secondary transfer potential in long-term stromal cell cultures and is thus postulated to contain all of the primitive hematopoietic stem cells in UCB. The in vivo transplantation potential of UCB was also measured. Ex vivo manipulated UCB progenitor cells were used to engraft irradiated human thymus fragments implanted in severe combined immunodeficiency (SCID) mice. Thymic engraftment with >5% donor-derived cells and a normal CD4/CD8 distribution was observed in 19 of 23 tissues tested. UCB cells from in vitro expansion cultures engrafted with efficiencies comparable to nonexpanded cells. Similar results were obtained for UCB engraftment of human bone fragments implanted in SCID mice. In all cases, engraftment was achieved in competition with endogenous competitor stem cells and across major histocompatibility barriers. Taken together, this data demonstrates that human UCB is a rich source of multipotent hematopoietic progenitors that can be cryopreserved, enriched by physical methods, and expanded in a limited fashion without measurable loss of long-term culture or in vivo engrafting potential as measured in these assays.

Animals↗

N-methyl-D-aspartate antagonists limit aminoglycoside antibiotic-induced hearing loss.

The use of aminoglycoside antibiotics is limited by ototoxicity that can produce permanent hearing loss. We report that concurrent administration of N-methyl-D-aspartate (NMDA) antagonists markedly attenuates both the hearing loss and destruction of cochlear hair cells in guinea pigs treated with aminoglycoside antibiotics. These findings indicate that aminoglycoside-induced hearing loss is mediated, in part, through an excitotoxic process. The high correlation (Spearman correlation coefficient: 0.928; P < 0.01) obtained between the relative cochleotoxicities of a series of aminoglycosides in humans and the potencies of these compounds to produce a polyamine-like enhancement of [3H]dizocilpine binding to NMDA receptors is consistent with this hypothesis, and provides a simple in vitro assay that can predict this aspect of aminoglycoside-induced ototoxicity.

Animals↗

A comparison of 600 and 200 mg mifepristone prior to second trimester abortion with the prostaglandin misoprostol.

OBJECTIVE: To compare the use of 600 and 200 mg mifepristone prior to second trimester termination of pregnancy with the prostaglandin misoprostol. DESIGN: A randomised study. SETTING: A Scottish teaching hospital. PARTICIPANTS: Seventy women undergoing legal induced abortion between 13 and 20 weeks of gestation. INTERVENTION: Administration of either 600 or 200 mg mifepristone 36 to 48 hours prior to prostaglandin. MAIN OUTCOME MEASURE: Induction-abortion interval. RESULTS: The geometric mean induction abortion interval was 6.9 (95% CI 5.8-8.4) h and 6.9 (95% CI 5.8-8.2) h in the 600 and 200 mg groups, respectively (no significant difference). The median dose of misoprostol was 1600 micrograms (three doses) in each group. Analgesic requirements and prostaglandin-related side effects were similar between groups. Overall, 11.4% of women required surgical evacuation of the uterus as a result of retained placenta. CONCLUSIONS: The dose of mifepristone used in second trimester abortion can be reduced from 600 to 200 mg.

Abortifacient Agents, Steroidal↗

Sustained retroviral gene marking and expression in lymphoid and myeloid cells derived from transduced hematopoietic progenitor cells.

The expression of antiviral genes in human hematopoietic stem or progenitor cells has been proposed as a strategy for gene therapy of AIDS. To be successful, this strategy requires safe and efficient transfer of the therapeutic gene into hematopoietic cells and gene expression has to be maintained in HIV susceptible cells following differentiation. We have used retroviral vectors to transfer the gene for a transdominant inhibitor of HIV replication (RevM10) into CD34+ stem/progenitor cells isolated from human umbilical cord blood (UCB). Following transduction, cells were allowed to differentiate either in vitro in clonogenic assays and long-term stromal cell cultures or in human thymus implanted in immunodeficient scid/scid mice in vivo (SCID-hu). Following differentiation and expansion, multiple lineages of cells were shown to carry the transgene. A higher percentage of gene-marked progenitor cells (10-30% in most cases) were detected in methylcellulose colony assays and in long-term stromal cell cultures (1-5%). In contrast, gene-marked T cells derived from transduced CD34+ cells in a SCID-hu model were detected at an even lower frequency (0.01-1%). RevM10 RNA expression was detected in CD34+ cells immediately after transduction and was maintained after in vitro differentiation of those cells into CD14+ myeloid cells. In T cells, the RevM10-specific RNA was detectable by RT-PCR and also by semiquantitative RNase protection. These findings demonstrate that LTR-driven gene expression is sustained in relevant cells derived from retrovirus-transduced hematopoietic progenitor cells after extensive differentiation in vitro and in vivo and suggest that stringent in vivo, rather than in vitro assays, may be a better preclinical system to improve gene marking and expression in hematopoietic cells.

Acquired Immunodeficiency Syndrome↗

Incongruent follicular development reduces gamete intrafallopian transfer pregnancy rate.

OBJECTIVE: To test the null hypothesis that asymmetric or incongruent follicular development does not influence GIFT pregnancy rates (PRs). DESIGN: A prospective comparative study. SETTING: Tertiary referral center for infertility. PATIENT(S): Ninety-three consecutive infertile patients having GIFT. INTERVENTION(S): Controlled ovarian hyperstimulation and GIFT. MAIN OUTCOME MEASURE(S): The incongruity ratio as a parameter of the asymmetry in follicular development and the clinical PR. RESULT(S): An inverse relationship was observed between the degree of incongruity and the clinical PRs. In patients with an incongruity ratio < 1.5, the clinical PR was 56.1%. In patients with an incongruity ratio > or = 1.5, the clinical PR was only 17.3%. CONCLUSION(S): Incongruent follicular development during controlled ovarian hyperstimulation has a marked negative influence on the outcome of GIFT cycles. Factors such as side of the gamete transfer and oocyte quality did not account for the observed differences.

Adult↗